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Biomedical subjects

C Fischer

Publications and source records attributed to C Fischer.

At least 289 records · Page 16Linked to original sources

Quantification of nitrendipine by stable isotope dilution and electron-capture negative ion chemical ionization.

The electron-capture properties of nitrendipine, a 1,4-dihydro-pyridine derivative with antihypertensive activity, have been applied to develop a sensitive and specific assay in biological fluids using capillary column gas chromatography and measurement in negative ion chemical ionization mode. The synthesis of a 13C4-labelled analogue suitable as a biological internal standard for bioavailability studies and of a 2H8-labelled analogue, which serves as internal standard, is described. The electron-capture positive ion chemical ionization and electron-capture negative ion chemical ionization mass spectra of nitrendipine and its isotope-labelled analogues are compared. The assay has a detection limit of 100 pg ml-1 plasma with a coefficient of variation of 10.2% using the selected ion monitoring mode and electron-capture negative ion chemical ionization. The method is specific, sensitive and accurate to determine terminal half-life times after intravenous and oral administration of nitrendipine and its 13C-analogue. From the nearly identical plasma concentration-time profile of nitrendipine and its 13C-labelled analogue, an isotopic effect can be excluded. Thus, the synthesized 13C4-analogue should be well suited as a biological standard for bioavailability studies.

Adult↗

The ulnar nerve as vascularized nerve transplant. Part I: Anatomy: arterial vascular supply.

The ulnar nerve is supplied basically by the arteries accompanying it in its various locations: in the axillary section, by a branch of the lateral thoracic artery or directly by the axillary artery; in the upper arm, by branches originating from the collateral ulnar superior artery; in the supracondylar section and in the region of the groove for the ulnar nerve, by branches originating from the anastomosis of the collateral arteries and the posterior branch of the recurrent ulnar artery; and in the forearm, by branches of the recurrent ulnar artery and the ulnar artery. Venous return is by the venae comitantes. Since the ulnar nerve possesses a good arterial supply, it may be used with different techniques as a vascularized nerve transplant in traumatic lesions of the brachial plexus, to repair more important missing nerve paths.

Axilla↗

Effects of salicylic and acetylsalicylic acid alone and in combination on platelet aggregation and prostanoid synthesis in man.

The present study was designed to investigate the effects of salicylate on the antiplatelet action of acetylsalicylic acid as well as on in vivo prostanoid formation and platelet function in healthy volunteers. In the first study six female volunteers received 350 mg acetylsalicylic acid intravenously, with and without previous oral administration of sodium salicylate (1200 mg daily for 3 days). Urinary prostanoid excretion as well as platelet aggregation and thromboxane formation were measured before and during salicylate and after acetylsalicylic acid. In the second study seven female volunteers received sodium salicylate (52.6 mg kg-1) or acetylsalicylic acid (60.7 mg kg-1) for 8 days in a randomized cross-over protocol. Urinary prostanoid excretion, platelet aggregation and thromboxane formation as well as salicylate plasma concentrations were determined before, during and after administration of each drug. Sodium salicylate did not impair the complete suppression of arachidonic acid-induced platelet thromboxane formation and aggregation obtained by the single intravenous dose of acetylsalicylic acid in the first study. Sodium salicylate in the second study did not affect urinary excretion of prostaglandin E2, its major urinary metabolite (7 alpha-hydroxy-5,11-diketo-tetranor-prostane-1,16-dioic acid), and 2,3-dinor-6-keto-prostaglandin F1 alpha, the main urinary metabolite of epoprostenol (prostacyclin, PGI2). In contrast, acetylsalicylic acid significantly decreased excretion rates of these prostanoids by 64, 59 and 61%, respectively. In both studies platelet aggregation and thromboxane formation induced by collagen, thrombin or arachidonic acid were not significantly affected by salicylate administration, whereas acetylsalicylic acid inhibited platelet aggregation induced by all three agents as well as thrombin- and arachidonic acid induced thromboxane formation.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Young children's recall and reconstruction of audio and audiovisual narratives.

It has been claimed that the visual component of audiovisual media dominates young children's cognitive processing. This experiment examines the effects of input modality while controlling the complexity of the visual and auditory content and while varying the comprehension task (recall vs. reconstruction). 4- and 7-year-olds were presented brief stories through either audio or audiovisual media. The audio version consisted of narrated character actions and character utterances. The narrated actions were matched to the utterances on the basis of length and propositional complexity. The audiovisual version depicted the actions visually by means of stop animation instead of by auditory narrative statements. The character utterances were the same in both versions. Audiovisual input produced superior performance on explicit information in the 4-year-olds and produced more inferences at both ages. Because performance on utterances was superior in the audiovisual condition as compared to the audio condition, there was no evidence that visual input inhibits processing of auditory information. Actions were more likely to be produced by the younger children than utterances, regardless of input medium, indicating that prior findings of visual dominance may have been due to the salience of narrative action. Reconstruction, as compared to recall, produced superior depiction of actions at both ages as well as more constrained relevant inferences and narrative conventions.

Child↗

[Biotransformation of alimemazine].

After application of alimemazine (1) 14 phenothiazine derivatives were detected in the rat urine. The structure of 9 metabolites was elucidated (TLC detection, UV, MS), which are hydroxy, N-dealkyl, S-oxide, and sulfone derivatives of 1. The hydroxy compounds, which are the main metabolites (greater than 50%), are partly conjugated. 5-10% of sulfones were observed. Some of the metabolites were detected in the feces, too. The relationship of the excretion products in urine and feces is 75:25%.

Animals↗

[Visual, early auditory and somatosensory evoked potentials in multiple sclerosis (917 cases)].

Visual (VEP), brainstem auditory (BAEP) and somatosensory (SEP) evoked potentials were recorded over a 6 year period in 917 patients with or suspected of multiple sclerosis according to Mc Alpine's criteria. Evoked potentials provided information of diagnostic relevance in detecting clinically unsuspected lesions (spatial dissemination). They also gave valuable informations in patients with atypical or borderline clinical features. When abnormal, VEP indicated clinically silent lesions in 45.1 p. 100 of patients with definite MS, 66 p. 100 of those with probable MS and 78 p. 100 of the possible MS. Less than 15 p. 100 of SEP and/or BAEP abnormalities were found in 83 patients with a simple or recurring retrobulbar optic neuritis. Thirteen patients with acute transverse myelopathy and no prior history of neurological disease were studied. All had normal visual and brainstem auditory evoked potentials. Abnormal VEPs helped to the clinical assessment of 88 patients with progressive spastic paraparesis 46,6 p. 100 of whom had abnormal VEPs demonstrating disseminated lesions and 36,1 p. 100 had abnormal BAEPs. The frequency of the various types of VEP, BAEP and SEP abnormalities was studied as well as their course on repeated recordings. Results of multivariate analysis are given. It was found that the longer the time interval between the first MS relapse and the evoked potential recording, the higher the incidence of abnormalities. The incidence of evoked potentials abnormalities was lower in patients with normal CSF and higher in patients with inflammatory CSF. The abnormalities were more frequent when patients had clinical evidence of lesions of the sensory pathways explored by the tests.

Adolescent↗

[Peroperative monitoring of early auditory evoked potentials].

Brainstem auditory evoked potentials (BAEP) were monitored during 37 neurosurgical operations (acoustic neurinomas with preoperative useful hearing, microvascular decompression of cranial nerves for hemispasm or trigeminal neuralgia, cerebellopontine angle tumors other than acoustic neurinomas, brainstem tumors and posterior circulation surgery). Intraoperative BAEPs were unchanged in 13 patients. Transient BAEP alterations (delay of I-V interval, transient obliteration of BAEP for as long as 8 minutes and 20 minutes) were seen in 13 other patients; irreversible BAEP alterations (loss of evoked response in 6 patients, delay of I-V interval) were seen in 11 patients. BAEP stability or alterations have been correlated with the ongoing surgical maneuver, the neurological outcome and the postoperative auditory function. BAEPs were found to be good predictors of post-operative auditory function but poorer predictors of neurological outcome. Some alterations are strictly associated with surgical retraction or with eighth nerve manipulation either immediately after the surgical maneuver or several minutes later. No detectable cause of BAEP changes was found in a few cases. The value of this monitoring is discussed. It may also help elucidate the mechanisms of hearing loss in acoustic neurinoma surgery.

Auditory Pathways↗

Simultaneous determination of 6-oxo-prostaglandin F1 alpha and 2,3-dinor-6-oxo-prostaglandin F1 alpha in biological fluids by stable isotope dilution and negative ion chemical ionization mass spectrometry.

A stable isotope dilution assay for the simultaneous determination of two metabolites of prostacyclin (1), 6-oxo-prostaglandin F1 alpha (2a) and 2,3-dinor-6-oxo-prostaglandin F1 alpha (3a), in human seminal fluid and human urine is described. A new chemical total synthesis of deuterated internal standard, 18,18,19,19-(2H4)-2,3-dinor-6-oxo-PGF1 alpha (3b), is presented and enables specific and sensitive quantification based on negative ion chemical ionization mass spectrometry. 2a and 3a were analysed as their methoxime pentafluorobenzyl ester tris(trimethylsilyl) ether derivatives in the selected ion monitoring mode registrating the [M-181]- fragments with a detection limit for both prostanoids of 10 pg per injection. The two metabolites occur in human seminal fluid in very low concentrations (2a: 2.8 ng ml-1; 3a: 1.7 ng ml-1) and cannot contribute significantly to the urinary metabolite levels which are in the range of 108-265 ng/24 h for 3a and 124-574 ng/24 h for 2a.

6-Ketoprostaglandin F1 alpha↗

Measurement of thromboxane B2 in human urine by isotope dilution and negative ion chemical ionization mass spectrometry.

A highly sensitive and specific assay for the quantification of thromboxane B2 (TXB2)(1) in human urine is described. The method is based on the use of low-blank (1H less than or equal to 0.2%) tetradeuterated internal standard 2 (18, 18, 19, 19-2H4-thromboxane B2), whose chemical synthesis is reported. After purification and high-performance liquid chromatography (HPLC) samples are derivatized to give an open-chain derivative of thromboxane B2, the methoxime pentafluorobenzyl ester tris(trimethylsilyl) ether (TXB2-MO-PFB-TMS3), most suitable for negative ion chemical ionization mass spectrometry. In the selected ion monitoring mode limits of detection per injection for pure standards and biological samples of 10 pg and 30 pg, respectively, are established. Normal urinary excretion of 1 in humans is 37-112 ng/24 h (n = 12).

Chemical Phenomena↗

Influence of intravenous acetylsalicylic acid and sodium salicylate on human renal function and lithium clearance.

The influence of intravenous acetylsalicylic acid (ASA; D,L-lysine-mono-acetylsalicylate), equimolar doses of sodium salicylate (SA) and placebo (P) on renal function has been studied in 6 healthy female volunteers, in 150 mmol sodium balance, and in lithium (Li) steady state with a plasma Li between 0.6 and 0.8 mmol/l. Following a bolus injection of 0.5 g ASA, 0.444 g SA or P (50 ml saline) given over 10 min and a subsequent continuous infusion of 1.5 g ASA, 1.332 SA or P (150 ml saline) over 170 min, urine was collected for 3 h as well as 6 plasma samples at 30-min intervals. Plasma ASA levels were between 13.8 and 22.1 micrograms/ml and for SA they were 20.8 to 82.6 microgram/ml during ASA infusion, and between 22.5 and 108.9 microgram/ml for SA during SA infusion. Neither ASA nor SA caused a significant change in urine volume, in the renal clearances of Na, K, free water, osmolality, creatinine, inulin and p-aminohippurate (PAH) or in plasma Li level. Renal Li clearance was slightly reduced by SA, from 37.8 to 29.4 ml/min (p less than 0.05). Since renal prostaglandin (PG) synthesis (urinary PGE2 excretion) was 60.6% suppressed by ASA and was not affected by SA, the decrease in Li clearance cannot be related to inhibition of cyclooxygenase in the kidney.

Adult↗

The acute deafness of definite multiple sclerosis: BAEP patterns.

Of 705 patients with or suspected of multiple sclerosis who underwent evoked potential recording during a 5 year period, 12 patients with definite multiple sclerosis experienced an acute hearing loss during a relapse of the demyelinating disease. Hearing loss was unilateral in all of the 12 cases but one; tinnitus was associated with hearing loss in 9 of the 12 patients. Deafness is an unfrequent symptom in the course of multiple sclerosis, being estimated to be no more than 3% in large series of multiple sclerosis. Brain-stem auditory evoked potentials were recorded in all 12 patients, during the relapse with acute hearing loss in 4 of them, after the relapse with hearing loss in the 8 others. During the relapse with hearing loss, BAEP abnormalities were present ipsilateral to the hearing loss in all 4 patients, wave I being absent in 2 of them. BAEPs were drastically improved when recorded after the relapse with hearing loss in 2 of the 3 patients in whom repeated records were made. BAEPs were abnormal on the side of the previous hearing loss in 5 out of the 8 patients recorded after the relapse with hearing loss. Clinical and BAEP data suggest that, in accordance with the anatomical organization of the auditory pathways, the lesion causing unilateral hearing loss in multiple sclerosis could be situated in the cochlear nerve or close to its entry zone in the brain-stem. However, dissociation between unilateral hearing loss and a normal peak I and I-III interval may occur.

Acoustic Stimulation↗

Dexamethasone effect on prostanoid formation in healthy man.

1. Dexamethasone was administered to six healthy female volunteers for 4 days, resulting in plasma levels of 4.8 +/- 1.4 x 10(-8) mol/l. Urinary excretions of six prostanoids as well as collagen-induced platelet thromboxane formation and aggregation were determined before, during and 1 month after administration of dexamethasone. 2. Dexamethasone had no effect on urinary thromboxane B2 (77 +/- 22 ng/day vs 63 +/- 16 ng/day during dexamethasone), dinor-thromboxane B2, the major urinary metabolite of thromboxane B2 (406 +/- 84 ng/day vs 380 +/- 90 ng/day), dinor-6-keto-prostaglandin F1 alpha, the major urinary metabolite of prostacyclin (199 +/- 41 ng/day vs 237 +/- 53 ng/day), tetranor-5,11-diketo-7 alpha-hydroxy-prostane-1,16-dioic acid, the major urinary metabolite of prostaglandins E1 and E2 (7712 +/- 1677 ng/day vs 7886 +/- 2565 ng/day) and tetranor-11-keto-5 alpha,7 alpha-dihydroxy-prostane- 1,16-dioic acid, the major urinary metabolite of prostaglandins F1 alpha and F2 alpha (14,394 +/- 2053 ng/day vs 18,288 +/- 2251 ng/day). Prostaglandin E2 excretion slightly but significantly increased from 217 +/- 48 ng/day to 294 +/- 55 ng/day. Collagen-induced platelet thromboxane formation and aggregation were not altered. 3. These results suggest that glucocorticoids do not regulate renal, platelet or total body prostanoid formation in healthy man.

Adult↗

[Antithrombin III--an important factor in long-lasting microvascular operations].

Antithrombin III is an important factor in preventing thrombosis in the normal coagulation system. The antithrombotic effect of heparin is closely related to the presence of Antithrombin III (AT III) as cofactor. It is also known that the concentration of AT III decreases considerably during long-lasting gynaecological procedures and in visceral surgery. We have found that the serum concentration of AT III also decreases during long-lasting microvascular procedures as in free flap or toe transfers. The crucial points are the duration of the operation, the duration of ischaemia of the extremity and the preoperative concentration of AT III which heavily depends on the general condition of the patient. In ten cases the AT III concentration decreased by an average of 21.7%. In three patients the AT III factor decreased below the critical level of 80%. In these cases levels between 60 and 65% were measured at the end of long microvascular operations. This decrease of AT III can be avoided by application of the AT III factor in an active form during the procedure (AT III in solution with heparin). To avoid thrombosis of the anastomosed vessels the local application of AT III in its active form before anastomosis has proved very effective. In practice, measuring of the AT III level has proved to be very useful in long microvascular procedures before the operation and at intervals of two to four hours. Nevertheless, in spite of AT III application careful microsurgical anastomosis has to be made.

Administration, Topical↗

A new slow-release form of 5-aminosalicylic acid for the oral treatment of inflammatory bowel disease. Biopharmaceutic and clinical pharmacokinetic characteristics.

A new enteric coated form of 5-aminosalicylic acid (5-AS, Salofalk) for the treatment of inflammatory bowel disease was developed. In 11 hospitalized patients with Crohn's disease or ulcerative colitis the steady-state pharmacokinetics of 5-AS and its major metabolite, N-acetyl-5-AS (Ac-5-AS), was investigated. During treatment with 0.5 g 5-AS tid elimination half-life (t 1/2) ranged from 0.7 to 2.4 h (1.4 +/- 0.6 h, mean +/- SD; n = 6) and mean steady-state plasma levels (Css) of 5-AS and Ac-5-AS averaged 0.7 +/- 0.4 micrograms/ml and 1.2 +/- 0.3 micrograms/ml, respectively. Treatment with the smaller dose of 0.25 g 5-AS tid (n = 5) resulted in a shorter t 1/2 (0.6 +/- 0.2 h), lower Css for 5-AS (0.4 +/- 0.2 micrograms/ml) and Ac-5-AS (1.0 +/- 0.2 micrograms/ml). Urinary and fecal recovery of total 5-AS was calculated to 44 +/- 21% and 35 +/- 10%, respectively. Both compounds were slightly bound to plasma proteins (5-AS: 43%, Ac-5-AS: 78%). In conclusion, the present data would suggest that the new oral dosage form delivers sufficient amounts of therapeutically active 5-AS for local and systemic action in patients with inflammatory bowel disease.

Adult↗